The structure/function relationships of two related proteins will be examined. Porcine submaxillary mucin is a glycoprotein containing about 67 percent by weight carbohydrate. Mucins lubricate the respiratory, gastrointestinal and urogenital tracts and protect epithelial cells from dehydration and injury. Much of porcine submaxillary mucin structure has been elucidated, but not all, including how the monomeric mucin molecules assemble to form dimeric and multimeric mucins that are the mature, functional molecules. The half-cystines that form the inter- and intrachain disulfide bonds in dimers and multimers will be determined. Particular attention will be given to the structural motif CGLCG and its role in assembly of multimeric mucin. These studies will utilize site-directed mutagenesis and expression of mutant constructs in animal cells in culture. Similar studies will be performed with norrin, a 133 residue human protein that is defective in Norrie disease, an X-linked, recessive human neurological disorder characterized by blindness, deafness and mental retardation. This protein is very similar structurally to the domain in some mucins that forms disulfide- linked multimers. The half-cystines in norrin that form inter- and intrachain disulfide bonds will be determined by the same methods used with submaxillary mucin. Hopefully, these studies will reveal how the disulfide-rich domains in proteins in which they occur lead to oligomer formation.